Liston Group

Liston Group
Liston Group

Research Summary

The Liston laboratory works on regulatory T cells. These are a type of white blood cell that act to suppress the rest of the immune response, preventing spontaneous autoimmune disease and acting as a rheostat to control just how active our immune system is. The number of these cells in our blood goes up as we get old, which may contribute to the immune-suppressed state of older persons. We seek to understand these cells, using both patient material and mouse models, so that we can harness their power to fine-tune the immune system for healthy ageing.
 

Latest Publications

Staels F, Lorenzetti F, De Keukeleere K, Willemsen M, Gerbaux M, Neumann J, Tousseyn T, Pasciuto E, De Munter P, Bossuyt X, Gijsbers R, Liston A, Humblet-Baron S, Schrijvers R Immunology

Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of IFN-γ immunity. The most frequent genetic defects are found in IL12 or a subunit of its receptor. IL23R deficiency in MSMD has only been reported once, in two pediatric patients from the same kindred with isolated disseminated Bacille Calmette-Guérin disease. We evaluated the impact of a homozygous stop mutation in IL23R (R381X), identified by whole exome sequencing, in an adult patient with disseminated non-tuberculous mycobacterial disease.

+view abstract Journal of clinical immunology, PMID: 35829840 13 Jul 2022

Whyte CE, Singh K, Burton OT, Aloulou M, Kouser L, Veiga RV, Dashwood A, Okkenhaug H, Benadda S, Moudra A, Bricard O, Lienart S, Bielefeld P, Roca CP, Naranjo-Galindo FJ, Lombard-Vadnais F, Junius S, Bending D, Hochepied T, Halim TYF, Schlenner S, Lesage S, Dooley J, Liston A Immunology

Interleukin 2 (IL-2) is a key homeostatic cytokine, with therapeutic applications in both immunogenic and tolerogenic immune modulation. Clinical use has been hampered by pleiotropic functionality and widespread receptor expression, with unexpected adverse events. Here, we developed a novel mouse strain to divert IL-2 production, allowing identification of contextual outcomes. Network analysis identified priority access for Tregs and a competitive fitness cost of IL-2 production among both Tregs and conventional CD4 T cells. CD8 T and NK cells, by contrast, exhibited a preference for autocrine IL-2 production. IL-2 sourced from dendritic cells amplified Tregs, whereas IL-2 produced by B cells induced two context-dependent circuits: dramatic expansion of CD8+ Tregs and ILC2 cells, the latter driving a downstream, IL-5-mediated, eosinophilic circuit. The source-specific effects demonstrate the contextual influence of IL-2 function and potentially explain adverse effects observed during clinical trials. Targeted IL-2 production therefore has the potential to amplify or quench particular circuits in the IL-2 network, based on clinical desirability.

+view abstract The Journal of experimental medicine, PMID: 35699942 04 Jul 2022

Liston A, Dooley J, Yshii L Immunology

Regulatory T cells (Tregs) control inflammation and maintain immune homeostasis. The well-characterised circulatory population of CD4Foxp3 Tregs is effective at preventing autoimmunity and constraining the immune response, through direct and indirect restraint of conventional T cell activation. Recent advances in Treg cell biology have identified tissue-resident Tregs, with tissue-specific functions that contribute to the maintenance of tissue homeostasis and repair. A population of brain-resident Tregs, characterised as CD69, has recently been identified in the healthy brain of mice and humans, with rapid population expansion observed under a number of neuroinflammatory conditions. During neuroinflammation, brain-resident Tregs have been proposed to control astrogliosis through the production of amphiregulin, polarize microglia into neuroprotective states, and restrain inflammatory responses by releasing IL-10. While protective effects for Tregs have been demonstrated in a number of neuroinflammatory pathologies, a clear demarcation between the role of circulatory and brain-resident Tregs has been difficult to achieve. Here we review the state-of-the-art for brain-resident Treg population, and describe their potential utilization as a therapeutic target across different neuroinflammatory conditions.

+view abstract Immunology letters, PMID: 35697195 10 Jun 2022

Group Members

Adrian Liston

Group Leader

Magda Ali

PhD Student

Meryem Aloulou

Visiting Scientist

Ronya Assady

Visiting Student

Pascal Bielefeld

Visiting Scientist

Orian Bricard

Visiting Scientist

Oliver Burton

Senior Postdoctoral Scientist

Francine Chenou

Visiting Scientist

Amy Dashwood

PhD Student

James Dooley

Senior Staff Scientist

Vaclav Gergelits

Postdoc Research Scientist

Keith Harrison

Visiting Student

Lubna Kouser

Postdoc Research Scientist

Miroslav Kratochvil

Visiting Scientist

Ntombizodwa Makuyana

PhD Student

Alena Moudra

Postdoc Research Scientist

Omar Shabana

Visiting Student

Samar Tareen

Visiting Scientist

Emily Thomas

Visiting Student

Daria Vdovenko

Visiting Scientist

Rafael Valente Veiga

Postdoc Research Scientist